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Human-Derived Organ-on-a-Chip for Personalized Drug Development

[ Vol. 24 , Issue. 45 ]

Author(s):

Yasamin A. Jodat , Min G. Kang, Kiavash Kiaee, Gyeong J. Kim, Angel F.H. Martinez, Aliza Rosenkranz, Hojae Bae * and Su R. Shin*   Pages 5471 - 5486 ( 16 )

Abstract:


To reduce the required capital and time investment in the development of new pharmaceutical agents, there is an urgent need for preclinical drug testing models that are predictive of drug response in human tissues or organs. Despite tremendous advancements and rigorous multistage screening of drug candidates involving computational models, traditional cell culture platforms, animal models and most recently humanized animals, there is still a large deficit in our ability to predict drug response in patient groups and overall attrition rates from phase 1 through phase 4 of clinical studies remain well above 90%. Organ-on-a-chip (OOC) platforms have proven potential in providing tremendous flexibility and robustness in drug screening and development by employing engineering techniques and materials. More importantly, in recent years, there is a clear upward trend in studies that utilize human-induced pluripotent stem cell (hiPSC) to develop personalized tissue or organ models. Additionally, integrated multiple organs on the single chip with increasingly more sophisticated representation of absorption, distribution, metabolism, excretion and toxicity (ADMET) process are being utilized to better understand drug interaction mechanisms in the human body and thus showing great potential to better predict drug efficacy and safety. In this review, we summarize these advances, highlighting studies that took the next step to clinical trials and research areas with the utmost potential and discuss the role of the OOCs in the overall drug discovery process at a preclinical and clinical stage, as well as outline remaining challenges.

Keywords:

Organ-on-a-chip, microfluidic technology, drug development, personalized medicine, human-derived induced pluripotent stem cells, tissue engineering.

Affiliation:

Division of Engineering in Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Cambridge, MA 02139, Department of Bioindustrial Technologies, College of Animal Bioscience and Technology, Konkuk University, Seoul 05029, Division of Engineering in Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Cambridge, MA 02139, Department of Bioindustrial Technologies, College of Animal Bioscience and Technology, Konkuk University, Seoul 05029, Division of Engineering in Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Cambridge, MA 02139, Division of Engineering in Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Cambridge, MA 02139, Department of Stem Cell and Regenerative Biotechnology, KU Convergence Science and Technololgy Institute, Konkuk University, Seoul, 05029, Division of Engineering in Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Cambridge, MA 02139



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